Current radiographic contrast media ("CM") are derivatives of triiodobenzene. Whether ionic or non-ionic, monomeric or dimeric, they are required to be stable compounds for their function. The in vivo stability is very desirable for an injectable diagnostic composition which should be excreted from the body unchanged. An ideal CM should then degrade in the environment into naturally recyclable components. With the current CM, even after very extended periods in sewage treatment plants, in ground water and in the oceans, the aromatic iodine remains firmly bound in these intact molecules. The approximately 3000 tons which are annually employed clinically, are quantitatively disposed of in the environment, where they increasingly accumulate. There is a growing concern about the potiential environmental impact of these "immutable" substances.
It has been previously suggested to collect and recycle CM, but the logistics, handling and the safety issues face insurmountable obstacles. It is therefore desirable to develop alternatives, such as contrast materials which have the desired in vivo properties, e.g. good stability and biological tolerance in the host, and which would when disposed of into the environment, be degraded.
Such compounds would have to fulfill the manifold requirements of the CM employed today. They would have to be economically feasible, having a simple synthetic procedure and inexpensive starting materials and reagents. They should be stable to autoclaving to provide a sterile CM. However, contrary to todays CM, following exposure to the environment and bacterial attack, the new CM would lose iodine and be degraded to benign products.
It is common knowledge that the triiodo-derivatives of 5-acylamidoisophthalic acid, such as the commercially available Iohexol, Iopamidol, Ioversol, Iodixanol, Iotrolan and Ioxilan are all extremely stable and upon UV irradiation in water or residence in sewage or soil, do not lose the iodine over extended periods. The same is true for the triiodo-3,5-diaminobenzoic acid, known as diatrizoate. All these compounds share acetyl acyl substituents, except Iopamidol, where the acyl substituent is lactoyl. Formyl has been avoided because of its assumed instability. However, novel stable CM employing formyl acyl subsituents have been previously disclosed, where appropriate N-alkylation of triiodoisophthalic formylamide products were found to be stable, but the product has not yet found commercial acceptance.